Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells
Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells
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DOI：
10.1016/j.stem.2015.03.002
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发表时间：
2015-05-07
期刊：
影响因子：
23.9
通讯作者：
Saitou, Mitinori
中科院分区：
文献类型：
--
作者：
Kurimoto, Kazuki;Yabuta, Yukihiro;Saitou, Mitinori
生殖细胞特化伴随着表观遗传重塑，其规模和特异性尚不清楚。在这里，我们定量描述了小鼠胚胎干细胞（ESC）诱导为外胚层样细胞（EpiLC）并从那里诱导为原始生殖细胞样细胞（PGCLC）过程中的染色质动态，揭示了染色质特征的大规模重组，包括H3K27me3和H3K9me2模式。 EpiLC 含有丰富的二价基因启动子，其特征是 H3K27me3 水平较低，表明处于分化准备状态。 PGCLC 最初从许多二价基因中丢失 H3K4me3，但随后随着 H3K27me3 的上调（尤其是发育调节基因）重新获得这一标记。 PGCLC 逐渐丢失 H3K9me2，包括在核纤层相关的核周异染色质处，导致核结构发生变化。在 PGCLC 规范期间，T 招募 H3K27ac 来激活 BLIMP1 和早期中胚层程序，随后可能通过 H3K27me3 的招募和扩散来介导 BLIMP1 介导的对广泛靶标的抑制。这些发现为重建种系表观基因组的调控网络提供了基础。
Germ cell specification is accompanied by epigenetic remodeling, the scale and specificity of which are unclear. Here, we quantitatively delineate chromatin dynamics during induction of mouse embryonic stem cells (ESCs) to epiblast-like cells (EpiLCs) and from there into primordial germ celllike cells (PGCLCs), revealing large-scale reorganization of chromatin signatures including H3K27me3 and H3K9me2 patterns. EpiLCs contain abundant bivalent gene promoters characterized by low H3K27me3, indicating a state primed for differentiation. PGCLCs initially lose H3K4me3 from many bivalent genes but subsequently regain this mark with concomitant upregulation of H3K27me3, particularly at developmental regulatory genes. PGCLCs progressively lose H3K9me2, including at lamina-associated perinuclear heterochromatin, resulting in changes in nuclear architecture. T recruits H3K27ac to activate BLIMP1 and early mesodermal programs during PGCLC specification, which is followed by BLIMP1-mediated repression of a broad range of targets, possibly through recruitment and spreading of H3K27me3. These findings provide a foundation for reconstructing regulatory networks of the germline epigenome.